Niemann-Pick type C1 (NPC1) is an autosomal recessive, neurodegenerative disease with a frequency of one in 120,000 live births. Approximately 95 percent of cases are caused by mutations of the NPC1 gene, and the remaining 5 percent are caused by mutations in the NPC2 gene. Mutations that produce defective NPC1 protein, a cholesterol trafficking protein, lead to accumulation of unesterified cholesterol and other lipids in lysosomes. Manifestations of the disease include neonatal jaundice, splenomegaly, ataxia and progressive neurodegenerative impairment of motor and intellectual function. Most often, the onset of symptoms occurs in early childhood, leading to death within a decade. Currently, no therapies have been approved by the FDA for this progressively fatal neurodegenerative disease. HPBCD has been shown to reduce both cholesterol and sphingolipid storage and to prolong survival in two types of Niemann-Pick type C1 animal models. The goal of this project is to provide the analytical and clinical tools needed to establish safe and effective dosing regimens for treatment of human subjects with HPBCD. TRND established an interdisciplinary project team of academic and industrial scientists from nine different organizations and received ongoing input from patient advocacy groups in order to accomplish the clinical evaluation of HPBCD most efficiently. TRND scientists conducted the animal toxicology studies necessary to file an Investigational New Drug (IND) Application with the FDA and helped support biomarker studies. TRND provided regulatory support to achieve clearance of the Investigational New Drug (IND) Application with the FDA in November 2012, and first-in-human clinical trials began in January 2013 at the National Institutes of Health (NIH) Clinical Center. These clinical studies are currently ongoing.